Infectious Diseases Flashcards
What are the Baseline investigations for all patients newly diagnosed with HIV?
- Confirmatory HIV test: HIV ELISA
- Serum HIV rapid test/ HIV non invasive test
- CD4 count
- HIV viral load (serum RNA)
- HIV resistance profile
- Serum western blot
- HLA B*5701 status
- Serology for syphilis, hepatitis B (sAg, cAb, sAb), hepatitis C, hepatitis A
- Toxoplasma IgG, measles IgG, varicella IgG, rubella IgG
- Other bloods: FBC, U&Es, LFTs, bone profile, lipid profile
- Schistosoma serology (if has spent >1 month in sub-Saharan Africa)
- Women: pregnancy test, annual cervical cytology
How does HIV present?
- Fever, night sweats > 1 month
- Skin rashes and post inflammatory scars
- Weight loss
- Oral candidiasis
- Diarrhoea > 1 month
- TB
- Karposi’s sarcoma
What additional testing may be required on samples of bodily fluids or tissues for suspected HIV patients?
- TB and MAI culture
- Fungal culture and PCR, fungal stains
- Cryptococcal antigen (CRAG - commonly performed in CSF if serum CRAG positive)
- Toxoplasma PCR
- Viral PCR (e.g. EBV, CMV, HSV, VZV, JC virus)
What are the RFs for HIV?
- Affected country
- IVDU
- Unprotected sex
- Perc. needle prick
How is HIV treated?
- No cure
- ARVs - NRTI - tenofovir, abacavir, NNRTI, protease inhibitors of integrase inhibitor
- Patients with low CD4 counts:
- PCP prophylaxis (if CD4<200) - Co-trimoxazole 480mg PO OD
- if CD4 <50 - Azithromycin 1250mg PO once weekly - protect against MAI
What measures should be taken for patients with low CD4 counts?
- If CD4<200 - Co-trimoxazole 480mg PO OD - prophylaxis against PCP.
- If the CD4 is <50 Azithromycin 1250mg PO once weekly - should also be given to protect against MAI
- CD4 <50 should - Ophthalmology with dilated fundoscopy to look for evidence of intra-ocular infections such as CMV retinitis
What vaccinations should HIV patients be given?
- Hepatitis B
- Pneumococcal
- Influenza yearly
What are some of the complications of HIV and what pharmacological agent can deal with this?
- TB: t: RIPE
- Karposi sarcoma;
- CMV/ CMV retinitis: ganiclovir
- Pneumocystic Jiroveci: co-trimoxazole
- Oral/ oesophageal candidiasis: fluconazole
- Meningoencephalitis
- Chronic meningitis: cryptococcus neoformans: amphotericin
- MAI: Mycobacterium avium infections
How is HIV transmitted?
Blood, sexual fluids, and breast milk
What is the pathophysiology of HIV?
- HIV binds, via its gp120 envelope glycoprotein, to cd4 receptors on helper t cells, monocytes, and macrophages
- These ‘CD4 cells’ migrate to lymphoid tissue where the virus replicates, producing billions of new virions.
- These are released, and in turn infect new cd4 cells.
- As infection progresses, depletion or impaired function of cd4 cells leads to ↓immune function.
What is used for PEP HIV?
- 1st-line pep6 in uk - Truvada® (tenofovir/emtricitabine)
- Raltegravir for 28 days
How does HIV present?
- Fever
- Lymphadenopathy
- Rash
- Cough/SOB
- Diarrhoea
- Abdominal pain
- Dysphagia
- ↑Liver enzymes
- AKI
- Headache/seizures/focal neurology
- Eye disease
What are some of the opportunistic infections in HIV and how are they treated?
- Pneumocystis jirovecii - progressive sob on exertion, malaise, dry cough. Haemoptysis and pleuritic pain rare. co-trimoxazole + prednisalone
- Tuberculosis - RIPE - rifampacin, isoniazid 300mg/ day
- Oral Candidiasis
- CMV Retinitis
- CMV
- Cryptosporidium: acute or sub-acute non-bloody, watery diarrhoea. Also cholangitis, pancreatitis
- Kaposi’s sarcoma: cutaneous or mucosal lesions: patch, plaque, or nodular. Visceral disease less common
- Lymphoma
What things should be considered when assessing patients with infection?
- Evidence
- Severity
- Patient factors
- Micro organisms
- Antimicrobial therapy
- Route of administration
- Any other treatment
- Risk of transmission to others
- Planning follow up and discharge
What questions should be asked for those with a fever in a returned traveller?
- Geographic region of travel
- Travel and duration
- Careful documentation
- Types of accomodation + rural vs urban stays
- Recreational activities + exposures
- Food and water consumed
- Sexual history, sexual exposure while abroad.
- PMH and predisposition to infection
What infectious diseases do you expect in the following time frames?
- 0-10 days
- 10-21 days
- >21 days
- 0-10 days: Dengue, rickettsia, viral
- 10-21 days: Malaria, typhoid, primary HIV infections
- >21 days: Malaria, chronic bacterial infections, TB, parasitis infections (helminths, protozoa)
What pre-travel immunizations and chemoprophylaxis should be given/ noted in a history?
- Vaccination: Hep A, B, typhoid, tetanus, childhood vaccinations (e.g. MMR) + yellow fever and rabies
- Malaria chemoprophylaxis (as directed).
- Personal protective measures e.g. insect repellent and bed-net use
What should be examined in clinical examination?
- Vital signs: HR
- Skin:
- A maculopapular rash
- Rose spots
- Necrotic ulcer
- Petechiae, ecchymoses, haemorrhagic lesions
- Eyes
- Splenomegaly
- Neurological system
What do each of the things examined in clinical examination indicate?
- Vital signs: HR
- Skin:
- A maculopapular rash: dengue fever, leptospirosis, rickettsia, infectious mononucleosis (EBV, CMV), childhood viruses (rubella, parvovirus B19), primary HIV infection
- Rose spots: pink macules, 2 to 3 mm in diameter) on chest or abdomen (typhoid fever)
- Necrotic ulcer: rickettsia (tick exposure)
- Petechiae, ecchymoses, haemorrhagic lesions
- Eyes: conjunctival suffusion - leptospirosis.
- Splenomegaly: mononucleosis, malaria, visceral leishmaniasis, typhoid fever, brucellosis.
- Neurological system: fever and altered mental status: meningo-encephalitis
What suggested investigations should be performed in patients with fever from unknown traveller?
- FBC, LFTs, U+E, electrolytes
- Malaria smears ± antigen detection dipstick: at least 3 times over 24-48 hours
- Blood cultures x2 (must have biohazard labels/travel documented)
- Urinalysis (± urine culture)
- Stool culture +/- stool for ova, cysts and parasites (OCP)
- CXR
- HIV, Hep B, Hep C and Syphillis (treponema) serology (white top)
- Acute serology tube to be saved in lab (white top)
What is malaria?
- Blood protozoa/parasite (plasmodium species) that is transmitted by night-biting Anopheles mosquitoes.
- P. falciparum results in the most serious illness.
- Approximately 90 percent of malaria cases originate in Africa.
- Other common species: P. vivax, P. ovale (mostly SE Asia)
How does malaria present?
- Abrupt onset of rigors
- High fevers, malaise, severe headache and myalgia, vague abdominal pain, nausea, vomiting.
- Diarrhea: 25 percent of patients
- Jaundice and hepatosplenomegaly
- Bloods: anaemia, thrombocytopenia, leukopenia, and abnormal LFTs
What are the complications of malaria?
- Hypoglycemia
- Renal failure
- Pulmonary edema
- Neurologic deterioration
- Leading to death
What investigations should be performed for malaria?
- Microscopy of thick and thin blood smear.
- Rapid diagnostic test (rdt) detection of parasite antigen. If malaria is suspected but blood film is negative: repeat at 12–24h and after further 24h
- Other: FBC (anaemia, thrombocytopenia), creatinine and urine output (aki), clotting (dic), glucose (hypoglycaemia), ABG/lactate (acidosis), urinalysis (haemoglobinuria).
What is typhoid fever?
- Typhoid infection is a faecal-oral transmissible disease caused by the bacterium Salmonella enterica, serotype S typhi.
- Common in many developing nations in South East Asia, Southern and Central America.
What are the symptoms of typhoid fever?
- Most important for diagnosis: dry cough, constipation, fever (stepwise, rising each day with progressive peaks)
- Other: Fatigue, headache, anorexia
- Abdominal pain, relative bradycardia (Faget’s sign)
- Symptoms arise up to 21 days after return
- Rose spots
- Diarrhoea (‘pea-soup’)
- Hepatosplenomegaly
What is found on physical examination of typhoid fever?
- Pulse-temperature dissociation
- Hepatosplenomegaly
- Rose spots
What are the laboratory findings for typhoid?
- Leucopenia
- Lymphopenia
- CRP
How is typhoid diagnosed?
- Stool, urine, bone marrow, blood cultures
- Bloods:
How is typhoid treated?
- IV Ceftriaxone 2g OD: give to patients who have grown s.typhi from stools
- Once sensitivities known, can switch to PO Ciprofloxacin 500mg BD, or PO Azithromycin 500mg OD.
What is the classical definition of patients with fever unknown origin?
- Temperature > 38 degrees on multiple occasions
- Illness of >3 weeks duration
- No diagnosis despite >1 week’s worth of inpatient
What are the common causes of pyrexia of unknown origin?
- Infective – tuberculosis, abscesses, infective endocarditis, brucellosis
- Autoimmune/connective tissue – adult onset Still’s disease, temporal arteritis, Wegener’s granulomatosis
- Neoplastic – leukaemias, lymphomas, renal cell carcinoma
- Other – drugs, thromboembolism, hyperthyroidism, adrenal insufficiency
What questions should be asked to a patient with pyrexia of unknown origin?
- Chronology of symptoms?
- Pets/animal exposure?
- Travel?
- Occupation?
- Medications?
- Family history?
- Vaccination history?
- Sexual contacts?
What else should be examined in PUO?
- Lymph nodes
- Stigmata of endocarditis
- Evidence of weight loss
- Joint abnormalities
What investigations should be performed for PUO?
- Blood: FBC/U+Es/LFTs/bone profile/CRP/clotting, TFTs, multiple sets of blood cultures, LDH, ferritin, B12, folate, immunoglobulins*, autoimmune screen* (RF, ANA, dsDNA, pANCA, cANCA, C3, C4)
- Micro/virology: HIV, Hepatitis B+C, syphilis, MSU, sputum cultures, malaria films*, atypical pneumonia screen*, viral swabs, CMV+EBV serology, Brucella serology*, Coxiella serology*, ASO titre*, fungal serology/PCR*
- Imaging: CXR, CT thorax/abdomen/pelvis, transthoracic echo, MR head*, MR spine*, radiolabelled white cell scans*, PET scan*
- Biopsies*:MC+S, TB culture, histology on all samples. Sites: Bone marrow, lymph nodes, abscesses, liver
What is the pathophysiology of TB?
- Caused by infection with Mycobacterium tuberculosis.
- Transmitted by aerosol inhalation and causes pulmonary infection, then spreads via haematogenous spread to anysite in the body
- Initial infection can be asymptomatic. Can lie dormant for many years without causing symptoms (latent TB), then reactivate later in life to form active infection.
- Common for people immigrating to the UK from endemic areas to experience reactivation after their arrival. ? Vitamin D
What is active TB?
- Occurs when containment by the immune system (t-cells/macrophages) is inadequate.
- It can arise from primary infection, or re-activation of previously latent disease.
- Transmission via inhalation of aerosol droplets containing bacterium. This means only pulmonary disease is communicable.
What is Latent TB?
- Infection without disease due to persistent immune system containment
- Assymptomatic
- Screening: CXR and measurement of interferon gamma (quantiFERON or T-spot)
How is latent TB treated?
- 3 months rifampicin and isoniazid or 6 months rifampicin alone
- Treatment reduces risk of reactivation needs to be balanced against the risk of hepatotoxicity.
- Pts > 35 - increased risk of hepatotoxicity. Guidelines advise against treating latent TB in these patients unless they have other risk factors (HIV or work as a healthcare worker)
What is quanti-feron and how does it aid diagnosis of Tuberculosis?
- Assesses the amount of interferon gamma released by T cells when they are exposed to proteins found on mycobacteria. Pre-exposed cells release more interferon
- It does not differentiate between active and latent TB.
- It is not used to diagnose active TB and can also be negative during infection.
- Patients with immunosuppression may not release interferon gamma causing false negatives
Who is routinely screened for TB?
- Immigrants from high prevalence countries
- Healthcare workers
- HIV positive patients
- Patient starting on immunosuppression
What are the common symtoms of active TB?
- Non-resolving cough
- Unexplained persistent fever (low or high grade)
- Drenching night sweats
- Weight loss
What are some of the signs of active TB?
- Clubbing
- Cachexia
- Lymphadenopathy
- Hepato/splenomegaly
- Erythema nodosum.
- Crepitations or bronchial breathing if there is pulmonary changes/pleural effusion.
- Pericardial rub if there is pericardial involvement (see below)
What are some of the investigations for active TB?
- Imaging: CXR, CT, MRI
-
Biopsy
- GOLD STANDARD: Culturing bacteria: Can take 6 weeks so ATT is usually started after samples taken
- Sputum acid fast bacilli smear
-
Pulmonary TB: sputum samples: X3 induced sputum (sputum taken after a nebuliser of 7% hypertonic saline)
- If a sputum sample is ‘smear negative’ then we usually proceed to bronchoscopy +/- EBUS (endobronchial ultrasound guided biopsy) of pulmonary lymph nodes
- Immunological evidence? Tuberculin skin test, quantiferon TB gold, T-Spot TB gold ?
How are Meningeal, lymph node, pericardial, GI TB diagnosed?
- Meningeal TB – lumbar puncture for TB culture and TB PCR
- Lymph node TB - core biopsy of lymph node (FNA is not adequate)
- Pericardial TB – ideally pericardiocentesis – often not practical
- Gastrointestinal – colonoscopy and bowel biopsy/ Ultrasound guided omentum biopsy
What does histology show for TB?
Caseating/necrotising granulomatous inflammation
When are steroids given for TB treatment?
If TB is affecting sites where additional swelling cannot be tolerated (e.g. meningeal/spinal/pericardial TB)
How is TB meningitis/CNS TB diagnosed?
- 1% of patients with TB have meningeal involvement.
- Lumbar puncture to exclude TB meningitis - high glucose, low glucose, lymphocytosis
- MRI - leptomeningeal enhancement
What are some of the complications of Pericardial TB?
- Complications: Pericardial effusion, Tamponade
- Pericardial rub/ kussmails sign
- 6 months treatment. Steroids given at the beginning
How does Miliary TB appear?
- CXR/CT
- It is widespread throughout the patient and is often found in multiple sites including CNS/bone marrow/pericardium.
What is used to diagnose disseminated/ Miliary TB?
- Neuroimaging (CT/MRI head)
- +/- lumbar puncture to exclude CNS
- Do not delay treatment whilst awaiting biopsies
- ATT is usually started as soon as it is determined whether or not there is CNS involvement
How is Multi-drug-resistant tuberculosis (MDR-TB) infection controlled?
- Negative pressure room
- Staff should wear masks/ PPE
How is TB treated?
- Standard ATT (Anti-TB Therapy): for all sites of TB except for CNS TB.
- Standard ATT: 2 months (intensive phase) Rifampicin +Isoniazid + Ethambutol + Pyrazinamide (available as a combined tablet called RIFATER) plus pyridoxine (vitamin b)
- 3 months (continuation phase): Rifampicin and isoniazid (combined tablet RIFINAH) plus pyridoxine
What are the side effects of anti TB therapy?
- Rifampicin: causes urine/tears to turn orange; drug induced hepatitis
- Isoniazid: Peripheral neuropathy (reduced by giving pyridoxine); Colour blindness; drug induced hepatitis
- Ethambutol: Optic neuropathy/ reduced visual acuity
- Pyrazinamide: Drug induced hepatitis +++
How is TB medication monitored?
- Before treatment: measure LFT and visual acuity (if using ethambutol)
- During treatment: monitor LFTS - if deranged treatment can either be stopped and the drugs gradually reintroduced once they have normalised, or a “liver friendly” regimen can be given (e.g. amikacin, levofloxacin and ethambutol) but the treatment duration is longer (up to 24 months)
What are the current infection controls for TB?
- Patients with non-resistant pulmonary TB should be nursed in a side room.
- After 2 weeks of treatment patients considered non-infectious to immunocompetent individuals.
- If the ward also manages immunocompromised patients, including HIV (i.e our ward!) then patients with respiratory TB need to be nursed in a side room until discharge regardless of whether they are smear +ve/-ve
- Smear +ve patients can still be discharged home but would need to quarantine themselves at home until they have completed 2 weeks of treatment.
- NICE guidance: staff do NOT need to wear masks/aprons unless MDR TB is suspected / they performing aerosol generating procedure e.g.nebuliser.
- Patients with smear +ve TB DO need to wear a mask when leaving their room until they have completed 2 weeks of treatment.
How is contract tracing performed for TB?
- Pt referred to TB nurses
- Contact test family: CXR + Quantiferon testing
- Treat any latent TB
How is HIV managed?
- Conservative: psychological support, safe sex, inform partner
-
Pharmacological:
- CD4<200 - co-trimoxazole 480mg PO OD
- CD4<50 - Azithryomycin
- Antiretroviral therapy regimen: bictegravir/emtricitabine/tenofovir alafenamide
- Dolutegravir: should be used with caution in women of childbearing potential and those who are trying to conceive